Stem cells, unlike differentiated cells have the capacity to divide and either self-renew or differentiate into phenotypically and functionally different daughter cells (Keller, Genes Dev. 2005; 19:1129-1155; Wobus and Boheler, Physiol Rev. 2005; 85:635-678; Wiles, Methods in Enzymology. 1993; 225:900-918; Choi et al, Methods Mol Med. 2005; 105:359-368).
Mesenchymal stein cells (MSCs) are multipotent stein cells that have documented evidence of therapeutic efficacy in treating musculoskeletal injuries, improving cardiac function in cardiovascular disease and ameliorating the severity of GVHD (Le Blanc and Pittenger, 2005). Being lineage restricted, they have limited but robust potential to differentiate into mesenchymal cell types, e.g adipocytes, chondrocytes and osteocytes, and have negligible risk of teratoma formation. Host immune rejection of transplanted MSCs is routinely circumvented through autologous or allogeneic transplantation. MSCs can be isolated from several adult tissues including bone marrow (BM), adipose tissues (ad), cord blood and expanded ex vivo.
However, availability of tissues for their isolation remains limiting and requires risky invasive procedures, and ex vivo expansion of MSCs while significant, is nonetheless finite.
The therapeutic capacity of MSCs to treat a wide spectrum of diseases in clinical and preclinical applications to treat a wide range of diseases [A1,A2] e.g. GVHD [A1] in musculoskeletal tissue bioengineering [A3,A4] and heart disease [A5,A6] has been attributed to their potential to differentiate into many different reparative cell types.
However, the efficiency of transplanted MSCs to differentiate into functional reparative cells in the injured tissues or organs, and in therapeutically relevant numbers have never been adequately documented or demonstrated.
This invention seeks to solve this and other problems with methods in the art.